Loss of basal forebrain p75NTR immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease
Document Type
Article
Abstract
The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75NTR), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75NTR-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75NTR-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75NTR CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD. © 2002 Wiley-Liss, Inc.
Keywords
Alzheimer's disease, Cholinergic, Dementia, Neurotrophin receptor, Nucleus basalis, Stereology
Publication Date
2-4-2002
Publication Title
Journal of Comparative Neurology
ISSN
00219967
Volume
443
Issue
2
First Page
136
Last Page
153
PubMed ID
11793352
Digital Object Identifier (DOI)
10.1002/cne.10122
Recommended Citation
Mufson, Elliott J.; Ma, Shuang Y.; Dills, John; Cochran, Elizabeth J.; Leurgans, Sue; Wuu, Joanne; Bennett, David A.; Jaffar, Syed; Gilmor, Michelle L.; Levey, Alan I.; and Kordower, Jeffrey H., "Loss of basal forebrain p75NTR immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease" (2002). Translational Neuroscience. 1863.
https://scholar.barrowneuro.org/neurobiology/1863